DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
The following continuity data is acknowledged in the present application file:
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Claims 1-4 are pending and before the Examiner.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 05 March 2025 has been acknowledged by the Examiner. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
The abstract of the disclosure is objected to because it does not commence on a separate sheet. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
In accordance with 37 CFR 1.72(b): A brief abstract of the technical disclosure in the specification must commence on a separate sheet, preferably following the claims, under the heading "Abstract" or "Abstract of the Disclosure." The sheet or sheets presenting the abstract may not include other parts of the application or other material. The abstract must be as concise as the disclosure permits, preferably not exceeding 150 words in length. The purpose of the abstract is to enable the Office and the public generally to determine quickly from a cursory inspection the nature and gist of the technical disclosure.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 4 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. The specification does not reasonably provide enablement for any person skilled in the art to use the invention for the treatment of all the recited cardiovascular conditions within the scope of this claim.
The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the application coupled with information known in the art without undue experimentation. (United States v. Teletronics Inc., 8 USPQ2d 1217 (Fed. Cir. 1988)). Whether undue experimentation is needed is not based on a single factor, but rather a conclusion reached by weighing many factors (See Ex parte Forman 230 USPQ 546 (Bd. Pat. App. & Inter. 1986) and In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988).
These factors include the following:
Nature of the invention.
The nature of this invention is drawn to a method of treating various cardiovascular conditions by administering to the subject a composition comprising the compound of claim 1.
The state of the prior art and predictability in the art.
The state of the prior art is that the pharmacological art involves screening in vitro and in vivo to determine which compounds exhibit the desired pharmacological activities (i.e. what compounds can treat which specific diseases and by what mechanism). There is no absolute predictability even in view of the seemingly high level of skill in the art. The existence of these obstacles establishes that the contemporary knowledge in the art would prevent one of ordinary skill in the art from accepting any therapeutic regimen on its face. It is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. In re Fisher, 427 F.2d 833, 166 USPQ 18 (CCPA 1970) indicates that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute.
Amount of guidance provided by Applicant and the presence or absence of working examples.
The Applicant has demonstrated within the application the use of the claimed compound but provided no working examples using the claimed invention. Particularly, the specification recites “the compounds of the invention are useful for improving cardiac (mechanical) [line 24, page 27], and useful as mitotropic agents [line 7, page 28]. However, there is no description as to how the recited diseases can be treated using the instantly claimed compound. Moreover, the disclosure does not provide how the uses covered by the claims are enabled. Various studies are required to enable compounds in clinical development; for example, development routinely relies on animal models in addition to iterative assays. Therefore, in the absence in vitro and in vivo testing, the treatment of all the cardiovascular conditions recited within this claim are not enabled for a skilled artisan.
The breadth of the claims.
The breadth of the claim is the treatment of selected species of cardiovascular conditions comprising administering a compound represented by formula (X), which there is no enablement provided.
The quantity of experimentation needed.
The quantity of experimentation needed is undue experimentation. One of skill in the art would need to determine what cardiovascular condition out of the multitude claimed would be benefited by the administration of the of the claimed compound.
The level of skill in the art.
The level of skill in the art is high, that of an MD or PhD capable of performing and analyzing a high throughput screen. However, due to the unpredictability in the pharmaceutical art, it is noted that each embodiment of the invention is required to be individually assessed for physiological activity by in vitro and in vivo screening to determine which compounds exhibit the desired pharmacological activity and which diseases would benefit from this activity. Thus, the specification fails to provide sufficient support of the broad use of the compound of the instant claim for the treatment of the various claimed cardiovascular conditions as a result, necessitating one of skill to perform an exhaustive search for which condition can be treated or prevented by the compound of the instant claim in order to practice the claimed invention.
Factors such as "sufficient working examples", "the level of skill in the art" and "predictability", etc. have been demonstrated to be sufficiently lacking in the instantly claimed methods. In view of the breadth of the claim, the chemical nature of the invention, and the lack of working examples regarding the activity of the claimed compound, one having ordinary skill in the art would have to undergo an undue amount of experimentation to use the invention commensurate in scope with the claim.
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. {In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)}.
Genentech Inc. V. Novo Nordisk A/S (CA FC) 42 USPQ2d 1001, states that "a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion" and "patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable".
Therefore, in view of the Wands factors and In re Fisher (CCPA 1970) discussed above, to practice the claimed invention herein, a person of skill in the art would have to engage in undue experimentation to test which disease can be treated by the composition encompassed in the instant claim, with no assurance of success.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-4 are rejected under 35 U.S.C. 103 as being obvious over Levin et al. (U.S. Patent No. 10556013; Filing Date: 20 June 2017) in view of Bose et al. (Trends Cell Biol. 2019 Sep;29(9):695-703; Publication Date: 31 May 2019).
The applied reference has a common applicant with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
Regarding claims 1 and 3-4, Levin et al. discloses compositions and methods for increasing efficiency of cardiac metabolism represented by formula (V):
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[col. 5, line 5-19]. In addition, it discloses that the compounds shift cardiac metabolism and promote mitochondrial respiration, making them useful therapeutic agents in treating heart diseases (e.g., heart failure, ischemic heart disease, and diabetic cardiomyopathies) [col. 2, line 9-14]. It further discloses that compounds that promote mitochondrial respiration may be an intermediate of the citric acid cycle or a molecule that can be metabolized to enter the citric acid cycle [col. 2, line 44-46]. However, the reference does not disclose compounds of Formula (V) where R11 is CH2COOH (acetic acid). Bose et al. discloses that in cells, acetic acid or acetate can influence mitochondrial respiration because it is converted to acetyl CoA by acetyl CoA synthetase, a central substrate for the Krebs cycle [page 1-2]. Therefore, it would have been obvious to one of the ordinary skills in the art to use acetic acid to promote mitochondrial respiration as disclosed by Bose and apply it to the compositions taught by Levin to arrive at the claimed invention with reasonable expectation of success in treating the various cardiovascular conditions instantly claimed because this modification aids in increasing the efficiency of cardiac metabolism.
Regarding claim 2, it is known in the pharmaceutical arts that the use of pharmaceutically acceptable excipients is employed in the drug development process to improve solubility, dissolution, stability, and administration of compounds. Accordingly, it would have been obvious to include a pharmaceutically acceptable excipient to the composition of claim 1 in order to administer the compound to the subject.
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-4 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 33 and 41 of copending Application No. 16365074, claims 39-40 and 45-46 of copending Application No. 19197314, claims 1, 11, 22, 42, and 54 of copending Application No. 18703512, claims 1, 8-9, 11, and 18-19 of copending Application No. 17922890, and claims 7-8 of copending Application No. 19196944, in view of Levin et al. (U.S. Patent No. 10556013; Filing Date: 20 June 2017).
Levin discloses compositions and methods for increasing efficiency of cardiac metabolism represented by formula (IV):
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, or R6 may be a substituent that promotes mitochondrial respiration such as an intermediate of the citric acid cycle or a molecule that can be metabolized to enter the citric acid cycle [col. 2, line 44-46], or a linker such as (CH2CH2O), or a NAD+ precursor such as nicotinic acid [col. 3 line 40-65]. In addition, it discloses that the compounds shift cardiac metabolism and promote mitochondrial respiration, making them useful therapeutic agents in treating heart diseases (e.g., heart failure, ischemic heart disease, and diabetic cardiomyopathies) [col. 2, line 9-14]. Therefore, it would have been obvious to try to modify the R6 position with either a molecule capable of entering the citric acid cycle, a linker, or a NAD+ precursor and arrive at the claimed invention with reasonable expectation of success in treating the various cardiovascular conditions instantly claimed because this modification aids in increasing the efficiency of cardiac metabolism.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-4 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 10953102, claims 1-2 of U.S. Patent No. 11844840, claims 1-2 of U.S. Patent No. 12318453 in view of Levin et al. (U.S. Patent No. 10556013; Filing Date: 20 June 2017).
Levin discloses compositions and methods for increasing efficiency of cardiac metabolism represented by formula (IV) with modifications at the R6 position as described above. Therefore, it would have been obvious to try to modify the R6 position with either a molecule capable of entering the citric acid cycle, a linker, or a NAD+ precursor and arrive at the claimed invention with reasonable expectation of success in treating the various cardiovascular conditions instantly claimed because this modification aids in increasing the efficiency of cardiac metabolism.
Conclusion
Claims 1-4 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CARINE P SEUDIEU SEUDIEU whose telephone number is (571)272-0459. The examiner can normally be reached Mon-Fri 8 AM - 4 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Murray can be reached at (571) 272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/C.S./Examiner, Art Unit 1626
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624
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